Huang T, Fang Z Z, Yang L
National Population and Family Planning Key Laboratory of Contraceptives Drugs & Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, China.
Pharmazie. 2010 Dec;65(12):919-21.
The aim of the present study was to investigate the inhibitory effects of medroxyprogesterone acetate (MPA) on four important UGT isoforms (UGT1A1, 1A6, 1A9 and 2B7). 4-methylumbelliferone (4-MU) was used as a nonselective substrate, and recombinant UGT isoforms were utilized as an enzyme source. The results showed that MPA exhibited inhibitory effects on UGT2B7 (IC50 = 29.3 +/- 1.5 microM), with a negligible influence on other UGT isoforms. The results obtained from Lineweaver-Burk and Dixon plots showed that MPA competitively inhibited UGT2B7. The Ki value was calculated to be 7.2 microM. Based on the concentration of MPA in human liver, the magnitude of in vivo drug-drug interaction (DDI) was predicted. The [I]/Ki value was calculated to be 0.31, which suggested that DDIs might occur when MPA was co-administered with drugs which mainly undergo UGT2B7-mediated metabolism.
本研究的目的是调查醋酸甲羟孕酮（MPA）对四种重要的尿苷二磷酸葡萄糖醛酸转移酶同工酶（UGT1A1、1A6、1A9和2B7）的抑制作用。使用4-甲基伞形酮（4-MU）作为非选择性底物，并利用重组UGT同工酶作为酶源。结果表明，MPA对UGT2B7表现出抑制作用（IC50 = 29.3 +/- 1.5 microM），对其他UGT同工酶的影响可忽略不计。从Lineweaver-Burk和Dixon图获得的结果表明，MPA竞争性抑制UGT2B7。计算得出的Ki值为7.2 microM。根据人肝脏中MPA的浓度，预测了体内药物相互作用（DDI）的程度。计算得出的[I]/Ki值为0.31，这表明当MPA与主要经UGT2B7介导代谢的药物合用时可能会发生DDI。
